IN VIVO #14 ENG by IN VIVO

Think health

No. 14 â&#x20AC;&#x201C; APRIL 2018

MENTAL ILLNESSES

BETTER UNDERSTOOD, BETTER TREATED JENNIFER DOUDNA Pushing the limits of science INSOMNIA New opportunities for sounder sleep MEMORISATION An elite-level sport Published by the Lausanne University Hospital (CHUV) www.invivomagazine.com IN EXTENSO THE MYSTERIES OF PUBERTY

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IN VIVO / NUMBER 14 / APRIL 2018

CONTENTS

FOCUS

11 / FEATURE Mental illnesses: better understood, better treated BY ERIK FREUDENREICH

MENS SANA

22 / INTERVIEW Jennifer Doudna: “I’m focused on pushing the limits of the technology” BY YANN BERNARDINELLI

26 / TRENDS Serial volunteers BY BLANDINE GUIGNIER

30 / DECODING Taking pain seriously

IN SITU

BY ALEXIA NICHELE

07 / HEALTH VALLEY

34 / DECODING New opportunities for sounder sleep

CURSUS

BY JULIEN CALLIGARO

43 / COMMENTARY

38 / PROSPECTING

Biological and cultural revolution

Memorisation: an elite-level sport BY PATRICIA MICHAUD

This young woman holds a sign that says “I have bipolar disorder, ask me anything” during the filming of a documentary in New York in the spring of 2017. Patients with mental illnesses are now being given greater consideration by society, as our feature explains (see p. 11).

44 / TANDEM Nurse Marie-Claude Boulet and physician Estelle Bezençon

IRA BERGER / ALAMY

CORPORE SANO

The difficulty of bringing medical devices to market

CONTRIBUTORS

BACKSTAGE FOCUS The persons interviewed for the feature on mental illnesses were shot with the following concept: portraits at chest height with the presence of one or both hands near the face.

CAROLE EXTERMANN Carole is an intern for LargeNetwork. For this issue, she investigated the difficulties of launching new medical devices to market (p.7).

SÉBASTIEN FOURTOUILL

LAURIANNE AEBY, DR

A long time contributor to “In Vivo”, Geneva based graphic artist Sébastien Fourtouill contributed to this issue’s layout design and helped research images.

Editorial

BIR

PATRICK DUTOIT

BÉATRICE SCHAAD Chief editor

As Yrwan, our young guide, leads us towards a volcano on the small Indonesian island of Flores, he explains how families are structured in his community. In families with multiple children, parents designate a boy or girl at birth. This child grows up knowing that he or she will be in charge of taking care of the parents when it becomes necessary. Parents raise their children, but they switch roles later in life when parents require assistance in their old age. Many healthcare systems incorporate family members in patient care. This approach is promulgated in Muslim cultures, where a term is used to describe the compassion, respect, and even patience one has for his or her parents: bir. China features a more authoritarian version of this same approach. Since 2013, the law has been used to correct children who flout the 24 rules of filial piety listed in texts that date back to the thirteenth century. According to the newspaper “La Croix”, a 77-year-old grandmother even won a suit on the matter. As a result, her daughter was ordered to visit her at least once every two months and during at least two Chinese festivals and holidays. The law for the “protection of the elderly” had been passed just before the trial against a backdrop of decreasing family unity, which the government is determined to combat. It’s clear that the role of friends and family members in the life of vulnerable individuals has long been an issue that a wide variety of cultures have had to tackle. The Swiss healthcare system is no exception. However, family members are too often a temporary presence in a hospitalised patient’s care plan. Their role is ill-defined, if they are involved at all. However, due to the rise of chronic disease and an ageing population, close friends and family members are increasingly becoming experts in the pathology of their parent, partner, or friend. This is well understood by the Department of Health and Social Action (DSAS), and its Social Insurance and Housing Department, which has long been involved in in-depth studies of the subject and is developing many initiatives for caregivers. The General Psychiatry Service of the Department of Psychiatry understands this dynamic well and has created a number of initiatives as well as a new position: the friends and family health liaison (see p. 18). Hospitals should follow this example and learn to integrate this new key player into their treatment plans if they want to fully account for their patients’ complexity and uniqueness. ⁄

Thanks to its university hospitals, research centres and numerous start-ups specialising in healthcare, the Lake Geneva region is a leader in the field of medical innovation. Because of this unique know-how, it has been given the nickname “Health Valley”. In each “In Vivo” issue, this section starts with a depiction of the region. This map was designed by Swiss graphic artist Romain Guerini.

IN SITU

HEALTH VALLEY Panorama of the latest innovations.

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IN SITU

HEALTH VALLEY

START-UP NUTRITION

Alver, which is turning to golden algae to fulfil the planet’s protein needs, was awarded the top prize at Frankfurt’s Start-up Innovation Challenge. For the Chardonne-based (Vaud) start-up, this freshwater micro-algae poses less of a threat to human health and the environment than meat, and is much more tasty and appealing than insects and traditional algae.

MOVEMENT

Eyeware received seventh place at the Swiss ICT Award. This Martigny-based start-up developed a technology to help paraplegics operate a computer mouse using head and eye movements, thereby allowing this group of people to use these essential tools.

ANDROLOGY

Comphya is one of the 20 winners of the European Venture Contest, in which over 1,250 start-ups participated. The Préverenges-based (Vaud) company developed an innovative treatment for erectile dysfunction aimed at patients who no longer respond to Viagra-type medication.

OPHTHALMOLOGY

RetinAI, a spin-off of UNIL and the University of Bern, won 130,000 Swiss francs during the final round of the 2017 Venture Kick. The award money will be used to make its software – designed to detect eye conditions that lead to blindness – economically viable.

“We decided to set up our first Swiss showcase at the heart of International Geneva, which also hosts a number of flagship organisations.” YONGLING DING CEO OF THE CHINESE PHARMACEUTICAL GROUP, BEIJING TONG REN TANG (BTRT), INTERVIEWED IN THE NEWSPAPER "LE TEMPS". A MAJOR PLAYER IN THE TRADITIONAL CHINESE MEDICINE INDUSTRY THAT EMPLOYS 30,000 PEOPLE AND GENERATES SOME 3 BILLION SWISS FRANCS IN REVENUE, THE GROUP OPENED ITS FIRST SUBSIDIARY IN SWITZERLAND IN DECEMBER.

Strengthening mitochondria to combat Alzheimer’s

NEUROSCIENCES Researchers at EPFL and scientists from the United States are turning to mitochondria, the powerhouse that provides cells – in this case, brain cells – with energy to fight against Alzheimer’s disease. In the brains of affected individuals, the mitochondria no longer function properly. The researchers first identified two natural cellular mechanisms that protect mitochondria when they’re healthy and recycle them when they’re defective, and then sought to activate them pharmacologically.

The sum (in millions of Swiss francs) pocketed by the Lausanne-based biopharmaceutical company AC Immune after Genentech, a member of the Roche Group, administered one of its Alzheimer’s disease antibodies to a patient for the first time as part of a phase II clinical trial. This is the second payment issued since the two companies started a strategic collaboration in 2012 regarding the use of anti-tau antibodies to treat Alzheimer’s and other neuro-degenerative diseases.

THE APPLICATION

GRIPPENET CH GrippeNET CH, which was designed by scientists from the ETH Zurich and the University of Geneva, lets users report their own flu-like symptoms to help improve the surveillance and modelling of the disease’s spread on a national level. In exchange for their anonymised personal data, participants receive information regarding the flu season in Switzerland, advice on how to stay healthy and the satisfaction of contributing to a civic-minded initiative for the common good. GrippeNET is the Swiss version of the European Influenzanet network, which proved that it could detect flu epidemics faster than traditional systems.

IN SITU

HEALTH VALLEY

FABRINAL, SWISSMEDIC

The difficulty of bringing medical devices to market Marketing technical medical devices is becoming increasingly difficult, especially for small companies. A closer look. REGULATIONS Cloé Houriet, director of the ocular technology company Fabrinal, has been trying for the past two years to market a new shunt designed to prevent ocular hypertension. However, her company has run into some hurdles. “The Swiss compliance evaluation body that we first contacted lost its accreditation. We had to start over from square one!” complains the director, whose company is based in La Chaux-de-Fonds. In the wake of the defective breast implant scandal involving French manufacturer Poly Implant Prothèse (PIP), the European Commission decided to tighten the requirements for marketing technical medical devices. This change primarily affected certification organisations, which are tasked with certifying the product’s compliance based on the risk category it falls under. “Because of the relatively small size of the Swiss market, the country’s regulations for all types of medical devices have to be in line with the regulations in the rest of Europe,” says Bernhard Bichsel, head of the medical device division of Swissmedic, the authority in charge of market surveillance for therapeutic products in Switzerland. As a result, the country must conform to this decision by revising the requirements for compliance evaluation bodies. These conditions are especially problematic for small companies like Fabrinal. “Major companies have teams in place to deal with these issues, whereas smaller businesses often have trouble managing such changes,” notes Bernhard Bichsel. Besides the additional human and financial resources that are required, companies also have a harder time obtaining the CE marking since the instrument being developed is entirely innovative and doesn’t have any equivalent on the market. Although Switzerland wants to obtain safer and better quality medical tools 7

TEXT CAROLE EXTERMANN

ABOVE: THE CANNULA DESIGNED BY FABRINAL, THE COMPANY MANAGED BY CLOÉ HOURIET, AND BERNHARD BICHSEL, HEAD OF THE MEDICAL DEVICE DIVISION OF SWISSMEDIC.

through these measures, they actually risk encouraging Swiss companies to move abroad. In fact, that’s what Cloé Houriet and her team decided to do when they selected a European organisation. “We chose the body that was most skilled in our field, ophthalmology, and picked one of the two largest to be sure we could complete the entire process,” explains the director. Despite the switch, the CE marking is still delayed because the organisation is being inundated with applications. In the United States, however, the certification procedure is faster. For this reason, Fabrinal decided to start selling its medical device there before trying to market it in Europe later on. The association Swiss Medtech, which helps protect the interests of Swiss medical technology, says it is assessing the situation. “There are only two certification bodies left in Switzerland, and it’s hard to say if they’ll remain,” explains Jorg Baumann, legal director and deputy manager of the association. In order to help young businesses market their products and comply with new regulations, Swiss Medtech created an information and discussion platform coordinated by Peter Studer, a senior regulations expert. The organisation plans on hosting seminars to offer start-ups guidance, thereby safeguarding and encouraging the Swiss medical technology industry. ⁄

IN SITU

HEALTH VALLEY

UNIL discovers a new disease

RÉMI QUIRION

COULD SWITZERLAND BENEFIT FROM HAVING A CHIEF SCIENTIST? EXPLANATION.

WHAT IS THE JOB OF THE CHIEF SCIENTIST OF QUEBEC?

This role was created in 2011 and includes several components. I advise the government of Quebec on research and innovation, manage the province’s three research funds and work to increase the visibility of Quebec’s scientists abroad – and those are just a few of the many hats I wear. If the government needs an opinion, it comes to me. I then consult with the scientific community to find an answer and communicate that information back to the government. Having a single contact person makes the process more efficient.

WHAT ARE QUEBEC’S RESEARCH PRIORITIES?

Eighty per cent of the research budget is awarded to non-targeted projects. We strive to support excellence in all fields. The remaining 20% is dedicated to the major challenges we face today, such as the consequences of climate change, the impact of artificial intelligence on society and the ageing of the population. Quebec is the world’s second oldest society after Japan. WHEN IT COMES TO RESEARCH, WHAT ARE THE TIES BETWEEN SWITZERLAND AND QUEBEC?

There are a number of collaborations between researchers. However, there isn’t a more general partnership, such as between the Swiss and Quebecker research funds, for example. We have partnerships with France and Belgium as well as with countries like Mexico and China. I would like to further our relationship with Switzerland. I completed an assignment in Switzerland in 2017, and I think there’s interest on both sides. / Rémi Quirion has been Chief Scientist of Quebec since 2011. Specialist in Alzheimer’s disease, schizophrenia and pain, he previously held various academic positions in the Canadian province.

2.3

3 QUESTIONS FOR

GENETICS The Integrative Genomics Centre at the University of Lausanne (UNIL) has identified the genetic cause of a previously unidentified disease that causes a serious brain malformation. Children with the condition either cannot eat or walk or die shortly after birth. Because the disease is very rare, the authors of the study collaborated with several countries to find cases. The research finally began in Lithuania with a family that had two children affected by the disease. The new pathology was named Alkuraya-Kucinskas syndrome in honour of the Saudi and Lithuanian doctors who identified the first patients. The discovery was published in January in the American Journal of Human Genetics.

The amount in millions of Swiss francs collected by the start-up GNUbiotics, based at BioArk (Monthey), during its first round of funding by private investors. The company develops dietary supplements featuring ingredients that are close to those present in breast milk, in an effort to combat obesity and intestinal infections. In addition to the human health market, the start-up is also targeting the pet food market.

KidsE: a video game for liver transplant patients

SERIOUS GAME KidsE, which is available on both computers and tablets, is designed to help children and teenagers who have received a liver transplant or are getting ready for surgery to better manage their disease and thereby increase their chances of a successful transplant. This applied game, designed by two professors from the Geneva-based Swiss Centre for Childhood Liver Disease (Centre Suisse des Maladies du Foie de l’Enfant), received the top prize from the 2017 Debiopharm-Inartis Challenge. In time, this game could be used to empower young patients undergoing other types of transplants or dealing with chronic disease.

IN SITU

HEALTH VALLEY

Cigarettes in the hot seat The noose is tightening around the tobacco industry, which has historically been welcomed in Switzerland. Study

The Swiss Lungs Foundation gave its 2017 Swiss Aerosol Award to Professor Reto Auer from the Bern Institute of Family Medicine and the Lausanne University Medical Polyclinic for conducting the first independent study on the IQOS e-cigarette from Philip Morris. According to this research, unlike the studies provided by the cigarette company, the IQOS e-cigarette does in fact emit toxic carcinogenic compounds similar to those released by traditional cigarettes and should not be exempted from the anti-smoking regulations in enclosed public spaces.

Second-hand smoke

Politics

The Swiss national railway system might ban cigarettes from all its stations by the end of the year. Tests are currently under way at six railway stations in Switzerland. Nyon started testing a fully smoke-free model in February, while NeuchĂ˘tel is trying out a less restrictive system by providing smoking "lounges". The national railway system should make a definitive decision this summer. In Europe, cigarettes are banned in railway stations in France, Italy, Austria, Spain, Belgium, and the Netherlands. Switzerlandâ&#x20AC;&#x2122;s railway system banned smoking on its trains in 2005.

Rebecca Ruiz, a Socialist Parliamentarian from Vaud, submitted a motion in December 2017 to ban the advertisement of tobacco products in points of sale to prevent cigarette manufacturers from targeting the children and teenagers who visit them. According to the bill, the expanding ban on tobacco advertising in cinemas and on posters has pushed the ads to points of sale, and especially street kiosks. One study found that nearly 80% of these shops, which are often visited by school children, contain advertisements for tobacco products. In nearly half of the cases, the images were placed near confectionery and treats, and were located at a childâ&#x20AC;&#x2122;s eye level.

Charging batteries with an eel

PAULO OLIVEIRA / ALAMY

BIOPHYSICS Researchers at the University of Fribourg worked with universities in the United States to study the mechanisms that allow an electric eel to produce a current. By basing their research on the fish, which uses the release of potassium ions and the uptake of sodium ions in specific cells to create voltage, they were able to produce electricity by using the difference in salinity between compartments of fresh water and salt water separated by ion-selective membranes. This research, published this past December in the journal Nature, could in time make it possible to recharge pacemakers or prostheses without surgery.

IN SITU

HEALTH VALLEY

BENOÎT DUBUIS President of Inartis Foundation

Harnessing group intelligence to tap into our region’s potential

People have an amazing capacity to use their imaginations and come up with new ideas. But how many become actual solutions that help make our day-to-day lives easier? Very few! You can change this by contributing to initiatives that rely on group intelligence. Group intelligence has become quite a buzz word nowadays, but how many people really use it? This approach could be used to breathe new life into all the founding principles of our society, from democracy and cognition to social interaction. The first step in that direction, which involves each and every one of you, is the power of social networks, which are literally revolutionising the ties between people.

However, group intelligence is still passive as it doesn’t extend beyond a simple reaction. This stage, which could be characterised as emotional, must slowly give way to an active, rational process based on distributed cognition. Such an approach is at the heart of a concrete regional initiative aimed at improving healthcare: the Debiopharm-Inartis Challenge. This programme represents a way to uncover new solutions and unlock the creative potential of civil society by giving new meaning to each person’s ideas. The goal is to support group intelligence. In a world where an interdisciplinary approach has become both a reality and a necessity, intellectual cooperation between people in an extraordinary technical environment offers a way to uncover disruptive and truly revolutionary ideas. This is a key part of working together to build our future.

It is with this mindset and the desire to offer The connections between individuals practical assistance to hospitalised people that create a network that determines a society’s the Debiopharm-Inartis Challenge was launched responsiveness to an event. When new types in February for the third year in a row. Particiof information and opinion leaders commupants will compete for a prize worth 80,000 Swiss nicate in a more targeted and accelerated francs (50,000 of which is offered in cash) based manner, a collective sense of empathy starts on the theme of “Patients’ quality of life during to emerge. This interconnectedness could be treatment”. Once again, the goal this year will be represented as a web made up of completely to find the very best ideas and support them until a artificial bonds of trust, in which the slightest prototype can be created. Entrepreneurs are shaping vibration can ripple to every corner. The easy our future using the strengths we have today. This availability of tools run by group intelligence, skill and energy belong to you and your network. such as Wikipedia, makes it possible to externalWe will need these invaluable resources to perform ise memory, relieve intelligence from the burden of having to remember, and offer it the possibility well and turn this initiative into a springboard for to transform itself, as Michel Serres has posited. innovative projects. Group intelligence is more than just a new way to access information. It also challenges the way Step away from the sidelines and become an active important information is selected, since the will participant in this movement. Submit your ideas and of the majority is the primary criteria. come away with concrete projects. ⁄ FURTHER READING

www.bioalps.org www.republic-of-innovation.ch

FOCUS

MENTAL ILLNESSES

Fluoxetine crystals. Better known by its commercial name Prozac, this substance discovered in 1974 is used in the treatment of depression.

MENTAL ILLNESSES

ANTONIO ROMERO / SCIENCE PHOTO LIBRARY

BETTER UNDERSTOOD, BETTER TREATED /

Even though mental disorders are frequent, they are still being treated too late. The development of more accurate detection methods and new medications could change this for the better. In this respect, the contribution of research is crucial.

/ BY

ERIK FREUDENREICH 11

FOCUS

MENTAL ILLNESSES

This could all change thanks to the discovery of biomarkers that are specific to mental illnesses. A biomarker is a measurement of the signals generated by the various biological processes within the human body. This is the principle behind measuring a person’s cholesterol levels or blood pressure, foreboding signs of heart disease.

ur brain contains anywhere between 85 to 100 billion neurons. Each cell is connected to 10,000 others, meaning information can be exchanged up to 100 trillion times at once. This complicated and dynamic network can malfunction, leading to mental disorders such as Alzheimer’s disease, depression, and bipolar disorder. These pathologies still occupy a special place in medicine, as explained by Jacques Gasser, head of the Department of Psychiatry at Lausanne University Hospital (CHUV), in this feature’s closing interview (p. 20). Diagnosing these diseases remains a complex issue and always includes a certain degree of subjectivity. The latest medications cause fewer side effects, but still focus on suppressing symptoms instead of treating them. Finally, medicine cannot prevent the onset of these diseases.

FIGURES

1,400,000 The number of people affected by mental disorders in Switzerland.

The percentage of young people suffering from mental illnesses.

Number of research axes within the Department of Psychiatry at CHUV: neuroscience, psychotherapy, human sciences, public health and epidemiology.

DETECTING MENTAL DISEASE EARLIER According to the Swiss Health Observatory, 18% of the Swiss population suffers from moderate to serious mental problems. Despite their frequency, these diseases are still being diagnosed too late. This is especially the case with psychosis. “Schizophrenia is often diagnosed two years after the onset of symptoms. A bipolar diagnosis can sometimes take up to 10 years,” explains Philippe Conus, head physician at the CHUV General Psychiatry Service. “However, several studies have shown that the greater the delay between disease onset and the start of treatment, the poorer the patient outcome.” Psychosis generally appears during the critical period of life at the end of adolescence and the start of adulthood. For this reason, CHUV launched the Treatment and Early Intervention in Psychosis Program (TIPP), which takes care each year of around 50 patients aged 12

However, identifying biomarkers in an organ as complex as the brain is far from easy. Nevertheless, like neurobiologist Kim Do Cuénod, scientists believe finding them is crucial (read point 2, p. 14). Biomarkers will make it easier to provide early treatment to people at risk of developing mental disease. They will also open the door to the development of objective diagnostic methods and new medications that are tailored to the needs of each patient.

18 to 35. This approach also raises ethical questions as society struggles to decide just how far these efforts should be allowed to go. “Our early intervention programme treats patients who are already showing clear signs of mental disease,” insists Philippe Conus. “The situation might be less clear with high-risk individuals, but these people are typically suffering from other issues, such as depression and anxiety, that require treatment. In this so-called prodromal phase, we use very low intervention strategies. At this point, we don’t prescribe neuroleptics and instead focus on psycho-social treatment.”

ALZHEIMER’S AND EMOTIONAL DISORDERS Early detection of mental disease also concerns the elderly population, observes Armin von Gunten, head of the University Service of Advanced Age Psychiatry (SUPAA) at CHUV. “People with a form of dementia such as Alzheimer’s disease also present with psychological disorders or behaviours, such as anxiety and depression. This often occurs at the early stage of the disease.”

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MENTAL ILLNESSES

“A BETTER UNDERSTANDING OF THE MECHANISMS OF THE DISORDERS IS NECESSARY TO DEVELOP NEW TREATMENTS” Philippe Conus believes that collaboration between the various branches of psychiatry is essential for advancing our ability to understand and treat mental disorders. BASED ON AN INTERVIEW WITH

O ERIK FREUDENREICH

in vivo What makes psychiatric research unique today? philippe conus We are in a phase in which our technological tools are allowing us to see things that have been invisible up until now, especially on a neurobiological level. Nevertheless, even if these advances are the source of much excitement, we can’t forget that each patient has a unique way of viewing the world. They might need a little bit of medication to see more clearly as well as some psychological help to approach things from a different angle.

we diagnose syndromes and groups of diseases; even though they look the same on the surface, they can come in several types with mechanisms that are completely different. A better understanding of these mechanisms is necessary to develop new treatments. That’s why an eclectic strategy is the right one. It has to be based on a mix of psychotherapy, neurobiology, and basic psychiatric care, in order to make use of advances in each of these areas. This shift is being made real with the hiring of researching clinicians, whose work is split between basic research and patient care. What progress has been made on developing new medications? pc The problem is that we do not know the mechanisms that are at the root of these diseases and that not everyone reacts the same to the same substance. This variable response is due to the fact that

iv Special attention is being paid to early intervention? pc Yes. Early intervention is now a focus for all mental disorders, and not just psychosis. To date, we cannot completely prevent the development of these diseases but we can either delay their emergence, attenuate their intensity or prevent development of secondary complications, which create the most problems in the patient’s life.

PHILIPPE CONUS IS THE HEAD PHYSICIAN AT THE CHUV GENERAL PSYCHIATRY SERVICE AND DEPUTY DIRECTOR IN CHARGE OF RESEARCH AT THE CHUV DEPARTMENT OF PSYCHIATRY.

LAURIANNE AEBY

ur understanding of mental disorders improves every year. More and more often, fundamental research is combined with studies on groups of patients, a translational approach “from bench to bed”. While the results are not yet immediately applicable, new practices, such as early detection of mental disease, are improving the lives of patients.

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MENTAL ILLNESSES

These problems, which can include verbal and physical aggression, can quickly become problematic for both loved ones and healthcare staff. “Up until now, Alzheimer’s research hasn’t looked at this aspect of the disease, focusing instead on discovering treatments to modify how it progresses.” That’s why Armin von Gunten and his team, in collaboration with the neurobiologist Ron Stoop, launched a study three years ago to identify the onset of these issues in patients suffering from the earliest stages of Alzheimer’s disease. One theory revolves around the role of ocytocin in forming personal attachments. “This hormone is a key factor in triggering uterine contractions during child birth and producing breast milk. It also influences the social ties between mother and child and, later on, between adults.” The idea is that ocytocin could improve the personal relationships of patients with cognitive disorders. “The study was carried out using a translational approach. Ron Stoop’s team worked on animal models. Their results were then compared to a cohort of patients,” says Armin von Gunten. “The preliminary analyses support our hypothesis. If this is confirmed, the next step would be to decide how treatment could be adapted to the social attachment profile of each patient.”

BASING TREATMENTS ON BIOMARKERS Translational research is also the weapon of choice of Kim Do Cuénod, head of the Psychiatric Neurosciences Centre at CHUV, who has recently been awarded the 2018 Outstanding Basic Science Award by the Schizophrenia International Research Society (SIRS). For the past 15 years, the neurobiologist and her team have been collaborating with the psychiatrists at CHUV to better understand schizophrenia. “Up until now, neuroscience most often focused on basic research. The results of these studies were difficult to apply to humans,” says Philippe Conus. “With Kim Do Cuénod, we wanted to answer clinical questions by rounding out observations on human patients with findings in animal models and vice versa. The work is very circular in nature.”

PROMISING RESULTS Their first study found that the brains of schizophrenic patients had a flawed antioxidant system. 14

New practices, new areas of expertise Zoom on four research projects carried out within the Department of Psychiatry at CHUV. TEXT: JUSTINE LIAUDAT, CÉLINE STEGMÜLLER, AND SOPHIE WOELDGEN

MEDICATIONS AND WEIGHT GAIN “The life expectancy of psychiatric patients is 10 to 20 years less than the general population,” explains Chin Bin Eap, director of the Unit of Pharmacogenetics and Clinical Psychopharmacology at Lausanne University Hospital (CHUV). One of the main causes is the use of second-generation antipsychotics. These medications often cause cholesterol and weight gain problems, which in turn lead to cardiovascular disease. “The analyses of psychiatric pharmacologists at CHUV indicate that patients being treated with these molecules experience a 5% increase in weight or cholesterol levels after the first month. This means patients could experience significant weight gain or have high cholesterol levels after one year.” In response to this data, the Psychiatry Service issued guidelines in 2007 to monitor the side effects of psychotropic drugs. As a result, a wide range of factors, including the patient’s cholesterol panel, waist circumference, and weight are measured at regular intervals as soon as treatment begins. “Tracking these predictive clinical values lets us intervene quickly,” says Alessandra Solida-Tozzi, senior physician in charge of the Minkowski section at the General Psychiatry Service. “The medical team can then provide recommendations about healthy life habits or change the patient’s prescription.” The next step in the research will focus on detecting indicators more precisely and developing clinical programmes aimed at minimising the risks associated with psychotropic molecules. CS

MENTAL ILLNESSES

LAURIANNE AEBY

FOCUS

“LISTENING TO SOMEONE WHO’S SUFFERING FROM PSYCHOSIS IS CRITICAL”

Ten years ago, Fribourg-native Blaise Rochat experienced a psychotic break. Today, he works to improve the relationship between patients and their entourage. “My life changed dramatically at age 46. I had a job and I was married with a child. In fact, I was working in the healthcare sector, first as a psychiatric nurse, then as a professor at the University of Applied Sciences and Arts in Fribourg. That’s when I experienced a series of setbacks, including a cancer diagnosis, septicaemia, and an emotional blow. I think these snow-balling problems led to my psychotic break. It resulted in hallucinations that became progressively worse with time. I started hearing voices and having conversations with them. Little by little, I walled myself off from the outside world. My interactions were limited to the hundreds of voices I heard in my mind. Eighty per cent of them were threatening. At some points during

my hallucinations, I was truly terrified. It was a really difficult time for me. The situation became untenable for my loved ones. When I was hospitalised, it seemed like I barely spoke with the staff. It was better around the time I received my diagnosis because I felt they were really trying to understand me. Once they put a name to it, it was as if the suffering I was experiencing on the inside suddenly became meaningless because it was just part of a hallucination. This acute period of my breakdown lasted around four years. When I started to feel better, I took stock of the damage. I went through a period of depression and doubt regarding my abilities and my identity. During this phase, I reached out to a patient association. I met people who accepted me for who I was and encouraged me to take up my responsibilities again. That really helped me regain confidence in myself and re-establish social ties. These days, I often give lectures

in classes for future healthcare professionals. I bring a dual perspective as both a patient and a former healthcare worker. I try to impress upon them the importance of listening to what the patient is going through. I also share my story on my website (editor’s note: experience-schizophrenique.ch) and at conferences for the general public. Once again, I insist on the importance of establishing a dialogue between patients, loved ones, and professionals. Right now, I have very few psychotic symptoms, but I still have doubts about how I would react and my ability to face a highly stressful situation. My story is unique and valuable – not in the least because my breakdown occurred at a later age than average. Still, it’s often a source of hope for the people who come to listen to me.”

MENTAL ILLNESSES

LAURIANNE AEBY

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“FRIENDS AND FAMILY NEED RECOVERY TIME AS WELL”

After her oldest son developed schizophrenia, Anne Leroy worked to improve the care provided to the friends and family of patients with psychiatric problems. “My son’s disease became apparent at the end of his studies at the School of Fine Arts in Sion. We think the trigger was a series of two emotional blows. The young woman he was living with left him, and she then committed suicide. After an initial hospitalisation that went well, Nicolas had to leave his apartment and move to a care centre, where things became hard very quickly. He went back to the hospital, and that’s when he decided to stop talking. He didn’t speak for over 10 years. To better understand his disease, I started talking with the other patients in the hospital. One thing led to another, and I began speaking with their loved ones as well. I saw that some family members were lonely and that the system was not providing them with adequate

information or treating them with respect. The staff were well versed in treating the disease, but not necessarily experienced in addressing the day-to-day trials of the family. That’s what gave me the idea to create a family support organisation. In October 2003, a dozen of us came together to form a working group. Family support groups go a long way towards shortening the time it takes to adjust to the diagnosis and learn about the illness. When a child has a serious accident, you can see him or her heal and recover slowly but surely. With mental illness, there’s a before and after. The disease often leads to a breakdown in communication between the patients and their loved ones. Friends and family can become disoriented. And just like the patient, they also need recovery time. Each person has to be given adequate space to regain their feet in their own time. Sometimes, it’s the patient who gives an important life lesson to his or her loved ones. In other cases, the patient’s friends

and family help him or her regain a sense of self-esteem. When we started our organisation, the participants were very receptive to getting together to talk. Over the past few years, they’ve wanted something much more personalised. Sometimes, we establish a relationship over the phone or through face-to-face meetings. This might go on for months before the person decides to take part in one of our get-togethers. We welcome all kinds of loved ones, including parents, brothers, sisters, partners, and friends. When speaking with mothers, one question that often arises is: ‘Will I be a grandmother one day?’ There are so many issues behind this one question. A lot of people find it hard to imagine that patients can live a satisfying life after their diagnosis. Nevertheless, it is possible!”

MORE INFORMATION: WWW.LILOT.ORG

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MENTAL ILLNESSES

After characterising the mechanisms in experimental models, the Lausanne-based researchers teamed up with scientists from Harvard University to study the effects of N-acetylcysteine (NAC), a general antioxidant medication, on the early stages of psychosis. “The results are very promising,” says Kim Do Cuénod. “In order to treat patients early, we need biomarkers that can help us identify people who are at risk of developing the disease. We observed that NAC improves neuro-cognitive function in a sub-

group of patients with a high level of oxidation in their blood.”

UNDERSTANDING EMOTIONS THROUGH PSYCHOTHERAPY

The next step will consist of verifying the effects of NAC on a larger group of patients. “Our study involved a cohort of 60 people. We’ll need to confirm it with a much larger number of patients, which is very expensive. We’ll also need to identify more specific targets and treat them. As a result, our research is designed to be a long-term project. I also dedicate some of my time to fund raising, especially through the Alamaya foundation.”

Psychotherapy has been shown to be effective in the treatment of personality disorders. This is the conclusion of a series of studies involving a group of young adults with borderline personality disorder that has been going on at the Department of Psychiatry at Lausanne University Hospital (CHUV) since 2010. “Right now, we don’t know a lot about why and how it works,” admits Ueli Kramer, privat-docent at the University of Lausanne and psychologist/psychotherapist at the Psychiatry Service who conducts psychotherapy research. “Still, psychological and biological changes can be observed during a single session and from one session to another.” Psychiatric follow-up care focused on diagnosing and managing the disease can be an integral part of treatment. However, when it comes to managing the issues associated with personality disorders, psychotherapy is the tool that’s the most useful right away. Patients make progress on multiple fronts, including an improved ability to regulate their emotions, establish a constructive relationship with their therapist, and achieve a better understanding of how they function. “We thought treating personality disorders was more a matter of addressing the patient’s psychological issues than their biological concerns,” explains Jean-Nicolas Despland, director of the University Institute of Psychotherapy at CHUV. Of course, medications are used, such as with specific depressive disorders, for example, but patients achieve real change through psychotherapy. CS 17

The study also shows that the medication improves structural and functional connections in the brains of these patients. The researchers then measured this progress using an electroencephalograph (editor’s note: an analytical method that measures the brain’s electrical activity). “These conclusions validate our strategy of using biomarkers to determine an appropriate treatment plan.”

NEW OUTREACH FOR LOVED ONES In addition to establishing a partnership with neuroscientists over the past 15 years, psychiatric care professionals have also changed how they relate to patients’ family members. “Before, they were generally seen as contributing to the patient’s problems,” explains Roland Philippoz, head nurse and healthcare manager at the General Psychiatry Service at CHUV. “Looking at loved ones as partners and recognising their suffering and difficulties has been a significant change – one that didn’t come easily.” What started as discussion groups at hospitals and outpatient clinics turned into support organisations for parents and loved ones of patients with psychotic, bipolar, or borderline personality disorders. “The underlying idea behind these efforts is to develop a community so people can reach out to each other and give voice to what they’re experiencing,” says Catherine Reymond-Wolfer, clinical nurse at CHUV and committee member of L’îlot, a Lausanne-based association for the loved ones of patients with mental disorders. Groups can also help rebuild bridges between the family and the healthcare staff. “Some mothers and fathers experienced physical or psychological vio-

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NEURAL IMAGING IN BALANCE Over the past few years, it’s become increasingly common for criminal trials in Europe and the United States to cite data from neural imaging technology. These tests round out traditional psychological expertise. However, the use of this data in criminal cases triggers various red flags, especially regarding the way the tests are perceived by the people involved in the trial. The research team from the Legal Psychiatric Institute at CHUV, led by Valérie Moulin, has analysed the effect of this data on court decisions. The team selected 62 Swiss and French magistrates, judges, and prosecutors, and then separated them into two groups. The first received a summary of psychiatric expertise including a written result of brain neuroimaging. The second received the same summary without this data. Integrated into a psychiatric assessment, the results of these examinations significantly modify the judges’ perception of judicial expertise (perceived as more objective, reliable, scientific, convincing, etc.) and the criminal responsibility of the defendant (assessed as less responsible). These results corroborate other studies showing the existence of cognitive biases in the perception of reasoning in the presence of neuroimaging data. For Valérie Moulin, neurobiology offers tremendous perspectives for understanding human beings and their behaviour. However, knowledge about violent behaviour is recent, often based on small, unrepresentative samples. But the magistrates tend to give them a higher value than the clinical data, perceiving them as free from subjectivity. The neurobiological markers give a concrete and representable character to a mental pathology for a magistrate, with the temptation to pass from the mind and its dysfunctions to the brain, while the hypotheses on this point are still fragile. Magistrates will have to learn about the use of this data and the experts to transmit this knowledge to a judicial body with major issues for the respect of freedoms and public safety. SW

MENTAL ILLNESSES

lence from their child for months or years before seeking help. The situation became too much, and now they no longer want to hear from their offspring,” says Roland Philippoz. “It’s sometimes easier to understand the disease from the perspective of family members of other patients.”

THE PARENTHOOD ISSUE Another major change took place this year in the form of a pilot project aimed at the children of people with mental disorders. The effort was launched by Christel Vaudan and Charlène Tripalo, a psychologist and a nurse in the Department of Psychiatry at CHUV. After creating a playroom where children could interact with their hospitalised parent and designating a representative to speak for the patients’ families, this initiative, called Famille+, focused on speaking with patients about parenthood. According to a recent study conducted in Winterthur, nearly 22% of people receiving treatment for a mental disorder have at least one minor child. “Up until now, this question wasn’t asked systematically,” says Roland Philippoz. “The goal is not to think of these kids as being at risk and diagnosing them, but rather to address the suffering they’re experiencing due to the amorphous nature of their parent’s disease. That’s why we wanted to focus on the idea of parenthood in order to have discussions with the children – as much as the patients allow.”

CONFIDENTIAL OR NOT Healthcare professionals quickly come up against the limits of doctor-patient confidentiality. In fact, it’s one of the topics highlighted through a series of events organised this year by the General Psychiatry Service. “On the one hand, patients often don’t want us to talk about their case, but on the other hand, families complain about being kept out of the loop. Establishing a constructive relationship without talking about important questions is very difficult. Being able to negotiate with the patient is critical to finding a solution to this impasse.” The event’s awareness-raising efforts are mostly aimed at staff. In the service, the average age on the teams is 29; most employees haven’t had children yet. “We want to promote an intergenerational perspective so parents aren’t stigmatised as ‘those people who make us crazy,’” says Roland Philippoz. “When you’re a parent yourself, you have a better understanding of the difficulties experienced by someone who’s the cause of so many challenges and the resources needed to support them.” ⁄

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CONNECTING TO TEENAGERS THROUGH MOBILE TEAMS “The goal of CHUV’s mobile teams is to establish a relationship by offering teens support and to provide local healthcare to people who otherwise wouldn’t be able to have such access,” explains Vanessa Baier, a nurse with the mobile team led by Dr Laurent Holzer of the University Psychiatry Service for Children and Adolescents (SUPEA).

treatment without first establishing a relationship with a member of the mobile team. “It’s a matter of addressing the young person’s needs and reintegrating the patient based on his or her mental issues and requirements, all while making sure he or she is on board with the process every step of the way.”

By meeting patients at their place of residence – family home or foster home – SUPEA professionals promote cooperation between primary care, which is in contact with patients, and outpatient or hospital units. Currently, they engage with about 50 adolescent patients.

Originally created to treat the adult patients in the psychiatric sector for the Lausanne region, the mobile teams gradually branched out to include young people as well. Over the past few years, the teams have added three other sectors. The SUPEA Research Unit works with mobile team clinicians to objectify the effectiveness of the The treatment can last “three to nine months, with proposed services and to model the trajectory generally one to two visits per week followed of patients in care. “It’s a question of understandby discussions with loved ones and educators,” ing for which types of patients this follow-up adds Baier. Ultimately, the goal is to redirect the by the mobile teams is the most effective and teenagers towards a traditional healthcare system for which other types of patients the care needs within a hospital or on an outpatient basis. The to be adapted,” explains Sébastien Urben, patients might have never accepted this form of head of the Research Unit. JL

The most common mental disorders DEPRESSION As far back as Hippocrates, medicine has sought a cure for depression, which the famous physician of ancient Greece referred to as melancholy. This disease is associated with both physical and psychological symptoms, including unusual fatigue, trouble sleeping, lack of appetite, low libido, constant feelings of sadness or negative thoughts, and the loss of self-esteem. Now more than ever, depression is a major public health problem. Estimates put the cost of the disease in Switzerland at over 10 billion Swiss francs per year. Nearly 25% of the Swiss population will suffer from severe depression at least once in their lifetime. SCHIZOPHRENIA Often incorrectly used to refer to multiple personality disorder, the term schizophrenia comes from two ancient Greek words: skhizein (break) and phren (thought). This mental disorder typically appears in young adulthood. Initial symptoms include a withdrawal from society and a break with reality. In the acute stage, this 19

type of psychosis triggers auditory hallucinations that can be highly disturbing for the patient. A multitude of factors contribute to the appearance of schizophrenia, including social, psychological, and genetic aspects. Nevertheless, medicine does not yet fully understand the causes of the disease, making it sometimes difficult to establish a precise diagnosis. BIPOLAR DISORDER People living with bipolar disorder experience cyclical patterns of intense euphoria and profound depression. In 1899, the German doctor Emil Kraepelin was the first to describe the modern conception of this disease, which was once called manic-depressive psychosis. During the depressive phase, patients feel sad and tired and are uninterested in the activities of day-to-day life. Conversely, during the manic phase of the disease, patients are full of energy and talkative, jumping from one subject to the next. They can also experience delusions and hallucinations. PERSONALITY DISORDERS Personality disorders include a wide range of maladaptive personality patterns. They can affect an individual’s cognition, feelings, or interpersonal relationships and cause suffering or

impede his or her ability to function in society. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the last word in psychiatry, identifies three major categories: eccentric disorders; dramatic, emotional, and erratic disorders; and anxious and fearful disorders. OBSESSIVE-COMPULSIVE DISORDERS The image most often associated with obsessive-compulsive disorder (OCD) is that of a person who washes their hands repeatedly. OCD is a type of anxiety disorder characterised by recurrent (obsessive) thoughts that the individual tries to relieve through specific rituals (compulsions). Affecting equal numbers of men and women and first appearing during both childhood and adulthood, OCD is the fourth most common mental disorder in the world. Because obsessive-compulsive disorder has a neurological component, it can be triggered by an infection of the central nervous system, such as encephalitis. Other neuro-degenerative diseases can also be associated with the onset of this pathology.

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INTERVIEW BY

GARY DRECHOU

MENTAL ILLNESSES

INTERVIEW “FROM DAY ONE, PSYCHIATRY WAS BASED ON THE SCIENTIFIC GOAL OF UNDERSTANDING HOW THE BRAIN WORKS.”

Jacques Gasser defends an approach that is both scientific and humanistic. He gives us a glimpse of what psychiatric care could look like in the future. Why is psychiatry seen as a “special case” in medicine?

in vivo

jacques gasser Psychiatry has always been a special type of medicine. It’s a medical discipline in that psychiatrists treat pathologies and diseases. But at the same time, it’s unlike other fields. When you break your arm, the injury is clearly identifiable. You receive treatment and your arm heals, regardless of whether you’re rich, poor, Muslim, or Catholic. In psychiatry, we can certainly identify a number of diseases, such as schizophrenia, depression and bipolar disorder, but the way they’re expressed changes depending on the context. Mental disease is “special” in that it affects the core of what makes us human. It disturbs our intentions, desires, will, beliefs – in short, our subjective experience. A bone, on the other hand, is not subjective. That might be true for the heart, but that’s another story! There are really two sides to our field. On the one hand, there’s the biological aspect, which places us firmly in the category of medicine (psychiatrists go to medical school, then complete an additional specialised programme). On the other hand, there’s also a subjective dimension, which makes psychiatry stand out from other medical disciplines.

Biography Pr Jacques Gasser, a specialist in issues related to the legal aspect of psychiatry, is the director of the CHUV Department of Psychiatry and the physician in chief of the Legal Psychiatry Institute. His publications include “Aux origines du cerveau moderne” (Fayard, 1995) and “Pour une psychiatrie scientifique et humaniste: l’école lausannoise” (Georg, 2011) in collaboration with Pr Patrice Guex. His latest work, “Le juge et le psychiatre”, written with the Swiss federal judge Jean Fonjallaz, was recently published under Stämpfli / Médecine et Hygiène. 20

Does this explain why psychiatrists sometimes describe their field as being outside the realm of science?

jg Yes, probably. After all, CHUV has only had a department of psychiatry for 15 years. Before, psychiatry was not only a separate speciality but also an entirely separate institution, with rather significant barriers. When we decided to join CHUV and to count ourselves among the rest of the medical field, most psychiatrists were proud to associate themselves with a larger institution and the academic world. However, others felt they were selling out to physical medicine and abandoning everything that made psychiatry special. Today, even though our integration has gone rather smoothly, some people continue to say we would work better if we were “off in our corner” and that we should focus more on this special field of medicine by emphasising its “specialness” as opposed to its “medical” nature.

In the past few years, especially with the rise of neuroscience, doesn’t it seem the balance is shifting more towards the “medical” end of the spectrum? Isn’t psychiatry taking a more scientific turn?

jg The turn happened when psychiatry started to be seen as its own branch of medicine at the beginning of the 19th century! From day one, psychiatry was based on the scientific goal of understanding how the brain works. The purpose of confining a certain number of patients, who prior to that point were considered crazy, in psychiatric asylums wasn’t to exclude or get rid of them, but on the contrary to include them in medicine – meaning understand them better and monitor them over time. The goal was to gradually reintegrate them into a dialogue-based society. All psychiatric categories were created by observing these patients. First and foremost, psychiatry is an attempt to communicate with human beings who, at first glance, seem com-

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pletely unable to communicate. Through these observations, we came to realise that we could communicate with even the “craziest” patients. iv

So there’s been no recent shift?

There was a major event in 1822. For the first time ever, doctors directly connected a psychiatric disorder, namely hallucinations, to a brain condition known as “general paralysis” at the time. A century later, we learned it was in fact syphilis. Tertiary syphilis causes encephalitis, a physical disease that can be clearly seen in the brain, which in turn leads to hallucinations. This discovery gave people a lot of hope. They thought, “That’s it! We’ve found it! Psychiatric disease comes from brain damage!” The problem is that no other similar discoveries were made for years after. Later, scientists found that Alzheimer’s disease presented clearly-identifiable cerebral pathologies that produced symptoms. What’s interesting, however, is that every time the origin of a disease was identified, it was based in neurology and shifted psychiatry more towards physical medicine. That’s still true of where we are now.

Is psychiatry turning into a branch of neuroscience?

jg In essence, the opposite is true. Clinical neuroscience is gradually becoming a part of psychiatry. We think neuroscience is something very new, but it’s actually following on from what came before. Neuroscience offers much more advanced analytical methods, and the vast amount of knowledge that results helps reduce the stigma surrounding mental disease. That’s why we created a Psychiatric Neurosciences Centre in the CHUV Department of Psychiatry. The centre’s research is really exciting because it has the potential to change our point of view. We’ve come to somewhat of an impasse with respect to how we understand the brain. Now is the time to think outside of the box – which is the hardest thing to do! At the same time, we’re taking care of patients every day and are obtaining pretty good results. The public isn’t really aware of it, but psychotherapies, for example, are some of the most effective treatments in medicine. 21

Jacques Gasser is head of the Department of Psychiatry at CHUV and professor at the Faculty of Biology and Medicine at University of Lausanne.

Isn’t there a disconnect between current treatments and the perception that our knowledge is continuing to improve and that the approach to psychiatry is increasingly scientific?

jg We do need to be careful to not promise too much. Transitioning from the laboratory to the clinic is still difficult. The reality nowadays is that there aren’t any results from neuroscience research that can be immediately applied to patients. It’s true that we’re getting closer and closer, and we will find things, but patients might not reap the benefits until many years down the road. iv

What will psychiatry look like in the future?

I think psychiatry will have to be framed differently – probably as a new branch situated between biology and subjective experience. Neuroscience might be what gets us there, in which case there will have to be a special kind of connection between clinical practice and neuroscience. We’ll need people who think differently – a bit “out of the box”. We’ll also need to continue our work in providing a continuum of care from child psychiatry and adolescent psychiatry to adult and senior psychiatry. Finally, connected objects will allow us to communicate even better with patients and their families. ⁄ jg

LAURIANNE AEBY

MENS SANA

Jennifer Doudna is now considered a candidate for a Nobel prize thanks to her work on CRISPR-Cas9.

MENS SANA

INTERVIEW

JENNIFER DOUDNA The American biochemist is one of the creators

of the breakthrough tool that allows genetic sequences to be edited. For In Vivo, she explains the technology, its applications and the resulting ethical challenges. INTERVIEW: YANN BERNARDINELLI

PHOTO: BRYAN DERBALLE / KINTZING

“I’m focused on pushing the limits of the technology” the body’s immune cells to aggressively and Eight years ago, Jennifer Doudna and her French colleague specifically target cancer cells as a way of Emmanuelle Charpentier put the final touches on an innovaimproving the body’s natural response. This tive technique that allows DNA to be edited with disconcertyear, scientists in several different countries ing ease and precision. Known as CRISPR-Cas9, this major will begin clinical trials using CRISPR-Cas9, breakthrough and the attention it has received have upset so we will watch anxiously as the boundaries of the quiet life of a researcher who grew up with the rhythms modern medicine are extended. of the Hawaiian surf. Doudna is now considered a candidate for a Nobel prize; she has founded three companies and is an active participant in the international ethiIV Can diseases with non-genetic origins be cal-legal dialogue on the potential consequences of this treated? JD In addition to cancer, researchers are new technology. Indeed, CRISPR-Cas9 may revolutionalso attempting to use gene editing to alter a body’s ise not only medicine but all of humanity. microbiome. Some health abnormalities are caused by an imbalance of bacteria in the body or the introduction of harmful bacteria. Researchers are working IN VIVO Scientists hope CRISPR-Cas9 may help to understand whether CRISPR-Cas9 proteins could rewrite flawed genes in people, opening tremenbe used to target harmful bacteria or use the bacteria’s dous new possibilities for treating diseases. own CRISPR-Cas9 system against itself as a way of What are the potential medical applications? self-destruction. Scrolling through the latest science paJENNIFER DOUDNA There is a wide range of exciting pers, I’m always amazed by the new and exciting uses of medical applications. Examples of genetic disgene editing that are being developed. eases that researchers are actively working to address include sickle-cell disease, muscular dystrophy, and cystic fibrosis. Researchers are IV What about xenografts? JD Xenotransplantation is the also deploying gene-editing technology to process of introducing cells or an organ from one species treat cancer. This procedure includes editing into another species. One use of gene editing in xenotrans-

MENS SANA

INTERVIEW

“GENE-EDITING TECHNOLOGY CAN HELP TREAT CANCER.”

and cut a sequence of DNA, the process takes considerable time and money. Rather than engineering a protein to bind to a specific sequence of DNA, CRISPR-Cas9 is programmed by a small RNA guide. Researchers are able to swap in different guides to target any DNA sequence of interest, which saves both time and money.

IV So, the only thing researchers have to do is generate the piece of RNA they like, and that’s an easy task with modern techniques of plantation is focused on growing human organs in pigs in gene synthesis. JD Correct. Targeting a sequence order to address the shortage of organ donors. This process requires altering the DNA of the pig to prevent an of DNA can be as simple as designing the correct undesirable immune response once the organ is implantRNA guide. The difficulties from this point vary ed into the human. depending on the application of the technology. If a researcher is interested in editing liver cells to address a particular genetic disease, they must IV Can CRISPR be used to make inheritable DNA overcome the hurdle of delivering Cas9 to those changes in embryos? JD Yes. If the DNA of an embryo cells. Researchers are also interested in using CRISis edited, then as the cells divide each cell will carry that PR-Cas9 gene editing to treat neurodegenerative edit. As the embryo develops and generates its own diseases, which may require introducing Cas9 into sperm or eggs, these cells will also have the same edited the brain. Designing the correct RNA is just the beDNA, passing down through future generations. ginning. There are many downstream questions that researchers are working hard to answer in order to IV CRISPR-Cas9 is a DNA editor. What does that achieve the full potential of this technology. mean? JD It means that with this tool we can precisely cut nearly any sequence of DNA in a wide range of organisms. We often use the word “edit” to IV CRISPR-Cas9 comes from bacteria. How do you describe this process because it draws parallels to transfer it to eukaryotic cells, tissues or entire orhow someone would edit a Word document on a ganisms? JD This is a question that many researchers computer. The Cas9 protein is bound to a small are actively investigating. The method of delivery deRNA guide as a way to program the protein to pends on the specific application. For example, scientarget a specific sequence of DNA. Once the RNA tists who are interested in treating sickle-cell disease identifies a complementary sequence DNA, attempt to remove stem cells from the body, then Cas9 is ready to make a cut. Such precorrect the disease-causing gene, and reincision gives researchers the opportunity to BIOGRAPHY troduce the cells back into the body. For American add or remove specific DNA sequences. Jennifer Doudna many other diseases, removing cells from This process resembles finding one word is a professor in the body is not an option. Instead, researchwithin an entire novel and changing one biochemistry and ers are developing ways to introduce Cas9 molecular biololetter in that single word. into the body and direct the protein to the gy at University correct cell. of California, IV Other gene editors, like zinc fingers, in Berkeley. In already exist. What makes CRISPR- 2012, in colIV Have researchers succeeded in modifyCas9 special? JD Partly the ease and af- laboration with ing genes in larger mammals like monFrench researchkeys? What are the technical limits? JD fordability of the technology. Although zinc er Emmanuelle finger nucleases can specifically recognise Charpentier, Researchers have succeeded in using CRIS-

she developed the gene editing tool known as CRISPR-Cas9. A discovery for which she earned many prestigious scientific awards ever since.

MENS SANA

INTERVIEW

general public about the potential consequences of gene-editPR-Cas9 gene editing in a wide range of oring technology and believe that the understanding and acganisms. Several larger members of the aniceptance of the technology as a strategy to better our society mal kingdom have had their genomes edited, is growing. including cows, dogs and chickens. In addition, this technology has been deployed to alter the DNA of plants. Technical limitations have arisen when editing plants because the outer walls of plant cells are significantly different from the membranes of animal cells. This has not stopped researchers from altering the DNA of several plants species, but considerable work lies ahead to edit the genomes of more plants. IV CRISPR comes from bacteria. Does this mean that biodiversity is crucial to future discoveries? JD Yes, IV Many scientists worry that this technology raises the possibility of creating a new human fundamental biology that focuses on a wide range of population with enhanced intellectual or physbiodiversity will likely continue to yield many exciting ical capacities. JD There are still many aspects of new discoveries. intellectual and physical capacities that we don’t understand, including specifics about how these IV This discovery was the fruit of a collaborative eftraits are coded in our DNA. Such “enhancement fort. Could the academic world do a better job of traits” are a product of many genes and also affectencouraging collaborations among researchers? JD ed by the environment outside the body. Before I’ve benefitted from many wonderful collaborations. making any attempt to enhance the human body, we Such work is encouraged by large collaborative grants need to fully understand these complicated traits. It’s and stimulated by working in proximity with other important that everyone be aware of these future fantastic scientists. In recent years, I’ve also had a possibilities, and I encourage a wide conversation chance to work closely with professors and experts in about such ethical issues. the humanities. Future collaboration between the sciences and humanities will be necessary to address many of the world’s most pressing problems. IV What are the risks for humans? JD Currently, CRISPR-Cas9 technology is not available to treat genetic diseases in humans or to make any desired enIV Are you pursuing your research at the Unihancements. The safety of this technology is still being versity of California in Berkeley? What’s the thoroughly tested. We have to continually test the safety future of the field? JD Yes I am, alongside many of CRISR-Cas9 to ensure a complete understanding of talented collaborators. An area I’m particularly any risks. excited about includes the investigation of anti-CRISPRs – small proteins naturally made by viruses to bind to CRISPR-Cas9 proteins and IV Do the potential consequences of your scientific disprevent them from binding or cutting DNA. covery haunt you like nuclear weapons haunted Einstein? JD It’s important for scientists to ponder and anticipate the potential uses of their discoveries and research. IV Such success is rare, especially for a bioI’m pushing for CRISPR-Cas9 to be used ethically and I’m chemist. How do you manage the global craze excited about this technology’s potential for improving hufor your discovery and your celebrity? JD I man health, engineering environmentally sustainable and am humbled by the interest in the technology nutritious food, and advancing scientific research. I’ve also and my journey. I continue to focus on pushbeen fortunate to participate in national and international ing the limits of the technology and increasdialogues with regulators, policy makers, ethicists, and the ing public awareness and engagement. ⁄

“I ENCOURAGE A WIDE CONVERSATION ABOUT ETHICAL ISSUES.”

TEXT BLANDINE GUIGNIER ILLUSTRATION OLA JASIONOWSKA

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TRENDS

SERIAL VOLUNTEERS Clinical trial volunteers play a crucial role in research. They agree to participate in studies for a variety of reasons, including medical, altruistic and financial incentives – with significant differences depending on the country in question.

undreds of thousands of people around the world volunteer every year to advance medicine. In India and the United States, where healthy subjects receive an actual salary in exchange for their participation, people tend to volunteer more for financial reasons than altruistic ones. According to the newspaper The Hindu, in the region around Bangalore, an Indian can receive 300 Swiss francs for participating in a therapeutic trial on melatonin. Also known as the sleep hormone, melatonin is an ingredient in a number of sleeping medications. This is almost three times the amount of the monthly minimum salary in this city. India is home to an increasing number of clinical trials according to the New Delhi Institute for Studies in Industrial Development. In 2008, 0.9% of trials took place in this south Asian country; this figure rose to 4.9% in 2013. The meteoric rise in inexpensive drug testing can be explained by three factors according to the Indian institute, namely “cheap human resources, the low cost of recruiting volunteers and the low amount

TWO TYPES OF STUDIES In observational studies, the volunteer is monitored by researchers without any kind of intervention. The purpose is to gather information on risk factors, lifestyles or the effects of exposure to a substance in the environment. The follow-up period can last several years. Interventional clinical trials are used to test treatments or procedures designed to prevent, identify or cure disease. The researchers “intervene” by asking the patient to undergo a diagnostic method or a surgical, radiation or medicinal treatment.

of compensation paid out in the event of injury or death.” SERIAL PARTICIPANTS IN THE UNITED STATES

Around 40% of all clinical trials in the world occur in the United States. 75% take place in private practices or commercial research centres. American volunteers often participate in multiple trials. Jill Fisher from the Center for Bioethics at the University of North Carolina followed 180 participants in phase I trials (see inset p. 28) for three years as part of the HealthyVOICES project. “Only 25% of the people included in the project were participating in a clinical trial for the first time, which is a very low percentage,” she explains. “Most were repeat volunteers. The trials represent their only source of income or act as a regular supplement when paired with part-time or seasonal work, for example.” The associate professor goes on to explain that the profile of American volunteers varies. However, the stereotypical volunteer is an African-American or Hispanic man between the ages of 30 and 50 with only a high-school education . As in India, “serial volunteers” in the United States mostly participate in

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TRENDS

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trials for financial reasons. “The volunteers are unsure at first. They are worried about their health and don’t want to get swindled. Once they see nothing bad happened to them and they do actually receive their $3,000 or $4,000 payment, the perceived risks for the second trial fall.” A STRICT FRAMEWORK IN SWITZERLAND

In Switzerland, the phenomenon of “serial volunteers” isn’t very common. Firstly, healthy volunteers who participate in clinical trials aren’t paid to do so. They are only reimbursed for the costs incurred due to their participation, such as transportation fees and the time spent doing the study. “Compensation varies between around 100 Swiss francs for a simple 30-minute meeting with a survey to 2,000 Swiss francs,” estimates Marc Froissart, director of the Clinical Research Clinic at CHUV. At the upper end of the spectrum, the studies require participants to spend several days or nights at the hospital under surveillance and take blood pressure tests, give blood samples, etc.” For example, participants in the test for the Ebola vaccine conducted in 2015 received 800 Swiss francs. Some Swiss residents, such as students or low-income individuals, participate in trials to make ends meet. “We shouldn’t kid ourselves – receiving an additional source of revenue is the primary motivating factor in most healthy volunteers.” Secondly, in Switzerland and in Europe in general, the number of trials authorised per subject is very low and more closely monitored than in the United States. “The regulatory framework in Switzerland was recently updated, especially with the law on human research that entered into force in 2014 and the 2002 law on therapeutic products. As a result,

DRUG TESTS Drug trials include four phases: 1: evaluate the medicine’s pharmacokinetic characteristics and safety, and identify side effects (10 to 80 people*). 2: find evidence of a beneficial effect and assess safety (100 to 300*). 3: determine if the treatment is clinically beneficial and/or better than previous treatments (500 to 20,000*). 4: After marketing, these studies are mainly focused on detecting rare adverse events (pharmacovigilance). * Number of patients is provided for informational purposes only

it is slightly more restrictive than in the rest of Europe,” says Marc Froissart. In January 2018, out of the 850 clinical trials that were listed on the Swiss National Clinical Trials Portal (SNCTP) platform, which includes all the studies in Switzerland that had been approved by ethics committees and put online by researchers, most involved subjects who already had a disease. The primary motivation for this type of volunteer is to benefit from medical breakthroughs. The law does not provide for any kind of compensation when the potential health benefits help the subject directly. At the Leenaards Memory Centre (CLM) at CHUV, researchers are pursuing a two-part goal focused on finding treatments that are effective against the lesions created by neurodegenerative diseases such as Alzheimer’s and stopping them before they lead to debilitating symptoms. “We explain to our patients who might want to participate in a study, as well as to their families, that medicine has not yet invented a cure for these diseases, only measures to help ease symptoms. Nevertheless, the possibility of helping to identify a potential treatment motivates quite a few people to volunteer.” Olivier Rouaud, a neurologist at CLM, has noted two other reasons why people participate in trials in addition to their altruism and their desire to help advance medicine. These individuals want to give themselves another chance at beating their disease or reducing the severity of their symptoms. Some volunteers also appreciate the regular hospital visits that are required by the research protocol. “They feel it helps improve their health because they’re monitored differently than in traditional healthcare environments.”

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OVER 6,000 PEOPLE IN LAUSANNE FOLLOWED FOR A GOOD CAUSE

This begs the question – how can you convince healthy people to participate in these scientific studies without offering them a financial incentive or the hope of a cure? “The Swiss are much more altruistic than we think,” says Martin Preisig, director of the Psychiatric and Psychopathology Epidemiology Centre (CEPP) and the psychological section of the CoLaus/PsyCoLaus study at CHUV. This observational study was launched in Lausanne in 2003. Its primary goal is to gather information on the links between cardiovascular diseases and psychiatric diseases as well as the causes of these conditions. “Unlike therapeutic tests, we simply observed a sample recruited from the general population of Lausanne, without affecting their daily lives,” Peter Vollenweider, acting director of the CHUV Internal Medicine Service and manager of the physical section of the study (see inset p. 26). Some 6,734 people aged 35 to 75 were selected at random in 2003 and asked to participate in the CoLaus/PsyCoLaus study. Participants then completed an initial interview that included a survey on their general health, cardiac health and family risk factors, as well as a clinical exam during which their vital statistics and blood pressure were measured and a blood sample was taken. Then, they were called in for a second interview designed to detect the presence of psychological issues (depression, addiction, etc.). The study has offered insights into the population of Lausanne. “The participants want to improve the state of medical research and help others,” explains Peter Vollenweider. The purpose of CoLaus/

The underrepresentation of women Women are traditionally under-represented in clinical trials. “The risk of pregnancy and the possibility of hormonal changes that could cloud the test results have long been used as justification for their exclusion,” explains Carole Clair, senior physician at Lausanne University Medical Polyclinic (PMU). The impacts of male-focused medicine are significant. “For example, the recommended doses for chemotherapy have sometimes proven to be incorrect for women, who are more susceptible to side effects like nausea. Aspirin, which was initially touted as an effective component of primary prevention for heart disease, is actually only beneficial for men.” Nevertheless, this imbalance is slowly correcting itself. “One of the requirements of the major European research project Horizon 2020 is to take women into account.”

PsyCoLaus is to gather information that will help improve the treatment and prevention of cardiovascular diseases and psychiatric disorders in the medium term. “These diseases are common. All of the volunteers have a parent, friend or colleague who has already been affected.” Participants also want information about their own health and to be reassured. “The first interview is like a check-up, and the results of the analyses are transmitted to the volunteers.” The study participants were called in again in 2009 and 2014. “We have to be able to see how the population’s health changes over the course of several decades,” says Martin Preisig. “We’ve also added other types of testing over time, including eye, pulmonary, sleep, cognitive function, and MRI exams, to name just a few.” After coming so far, the team has no intention of stopping. “We will soon ask the children of the volunteers to participate. The goal is to determine the prevalence of risk factors for cardiovascular and psychiatric disorders in younger subjects between the ages of 15 and 35 and study the factors governing the transmission of these diseases in families. We are very thankful for the help provided by the Lausanne population.” ⁄

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Taking pain seriously Though pain was once considered a consequence of a pathology, the medical profession now recognises it as a separate problem that requires specific treatment. TEXT: ALEXIA NICHELE

ccording to a study by ANOTHER WAY OF THINKING ABOUT PAIN Pain Alliance, around Even thinking about pain as an individual 20% of the European experience represents a change. “After population suffers from a painful stimulus occurs in the body, chronic pain, whether the brain interprets the signal based in the form of back on past experiences, the context of the pain, neurological pain situation, the person’s mood as well as or pain caused by cancer, that decreases their culture and education,” explains the quality of their daily life. This problem Yolande Kottelat, director of the is so widespread in fact that pain is now Institutional Pain Programme at CHUV, considered a disease requiring its own which was created in 2007. “Our role treatment plan. There is an increasing as professionals is to legitimise this number of medical centres subjectivity and offer personaldedicated to pain manageised strategies.” Nowadays, What ment. These facilities employ the universal definition of is pain? a multi-disciplinary approach pain (see inset) also includes that uses medicine, physical an emotional dimension that Official therapy and complementary is just as important as the therapies such as acupuncsensory aspect. definition ture and hypnosis. Despite Pain comes in various the progress made in the past As a result, suffering is difficult forms and intensity few years, the effectiveness to objectify. However, this levels, and lasts for different amounts of of treatment remains limited isn’t the goal. “We accept that time. Many definitions in some cases, in particular each person has a different have been developed, because pain is a complex experience of pain, even if we but there is actually a mechanism that is experienced don’t always understand why,” universal definition of subjectively. says Marc Suter, an associate pain. The International Association for the Study of Pain (IASP) defines it as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”

Acute pain Acute pain is a symptom caused by a potentially harmful stimulus. It is considered useful because it alerts the body to the danger of a potential or real injury or any other pathological process. By treating this type of pain immediately and aggressively, such as after an operation, the risks of it developing into a chronic condition are reduced.

DECODING

physician with the Pain Treatment Centre at CHUV. “Useless suffering is unacceptable.” Even though patients are listened to more closely, the therapeutic tools that are currently available are sometimes not enough. “Chronic pain, especially neuropathic pain, is particularly resistant to known treatments.” As for results obtained through research, their clinical application remains unsatisfactory. THE RULE OF COMMUNICATION

“As much as possible, we encourage the patient to provide us with a maximum amount of information about their pain starting from day one of their treatment,” says Yolande Kottelat. To do this, various evaluation tools have been developed, starting with verbal, visual and numeric

The “Dolografie” project was created last year by two Bern-native graphic artists to help patients express their pain when words aren’t enough. It’s made up of a set of 34 cards, each of which illustrates a feeling.

scales ranging from 0 to 10. More recently, doctors have started using diagrams that help patients pinpoint their pain and a survey that lets them provide qualitative, sensory (burning, radiating, etc.), and emotional (worrying, all-consuming, etc.) information. For patients who cannot communicate, the observation of clinical signs, such as cardiac frequency, pupil dilation and a behavioural scale can be used. In the case of chronic pain, healthcare professionals agree that a treatment’s effectiveness can be evaluated by looking at its impact on quality of life, and not just on the patient’s level of suffering. Anxiety, depression and quality of life scores are systematically analysed and patients’ perception of pain in their day-to-day lives is taken into account as a whole. “The patient can be caught up in a vicious circle,” adds the director. “Anxiety, stress and the lack of sleep increase pain and vice-versa.” The result

2018 AFFOLTER / RÜFENACHT, BERN

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is a challenging ordeal – nearly half of all patients with depression are in pain and up to 40% of people with chronic pain go through periods of depression. “It’s critical to provide the patient with relief as soon as possible to avoid a cascade of adverse effects.” Indeed, another risk is prolonging the hospitalisation of patients who are recovering from surgery. MEDICATION IS NOT THE ONLY SOLUTION

Up to 10% of patients develop a debilitating pain after surgery. To diminish post-operative pain, special pumps allow patients to self-administer morphine or local anaesthesia intravenously. For the past few years, ultrasound can be used to place a catheter or inject anesthetic medication much more precisely.

World Health Organization (WHO). Some antidepressants and antiepileptics, adjuvants commonly prescribed to treat neuropathic pain, decrease pain by 50% in only one out of every three patients according to a study by doctors from the International Association for the Study of Pain (IASP). However, these medications have a lower risk of addiction than opioids. Moreover, few truly innovative pain medicines have been invented in the past 15 years. “We need new medication targets and better prevention,” says Marc Suter. ON THE RIGHT PATH

Every year, the International Association for the Study of Pain (IASP) launches a global campaign against pain. In 2017, the organisation focused its attention on post-operative pain, which affects all There are other tools to reduce acute or surgical patients. More generally, pain persistent pain in addition to drug therapy management has become a holistic field and psychotherapy or physiotherapy. of medicine that takes into account the Targeted injections, acupuncture, overall well-being of the patient. “We relaxation therapies (yoga are on the right path,” says or meditation) and electric Yolande Kottelat. “We are tryChronic neurostimulation are also ing to expand our therapeutic pain effective tools against pain. arsenal while still maintaining Patients who practise hypnosis a customised approach for Pain is considered chronic when it lasts are able to better manage their each patient.” The 2018 theme longer than three pain and receive less mediof the IASP campaign is pain months. It can be inflam- education. This implies better cation. In addition to these matory (as a result of non-exclusive treatments, training of caregivers and paosteoarthritis, for the therapeutic relationship example) or neuropathic tients, but also informing poliis crucial. When this relationcy makers and decision-makers (due to a nerve lesion). Neuropathic pain is the ship is positive, the body and of the need to further improve hardest to treat because pain management and to mind react well to the medical it responds relatively act in itself. It is one of the continue research to better poorly to even powerful components of the famous understand it. ⁄ pain treatments. In placebo effect. these situations, certain Nevertheless, pain medicine is at the top of the list of the treatment protocol and is adjusted based on ranges of intensity established by the

antidepressants and anti-epileptics can be administered. Chronic pain affects around a fifth of the population and seriously deteriorates the quality of life of the people suffering from it. The 11th Revision of the International Classification of Diseases, which is scheduled to be published in May 2018, lists chronic pain as a diagnosis for the first time.

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COMMENTARY

SAMIA HURST Director of the Institute of Ethics, History, and Humanities (iEH2), Faculty of Medicine, Geneva

How to better handle ethical problems A wide variety of questions are asked during clinical ethics consultations, but certain issues come up again and again. For example, we might be asked, “How much is too much?”. This question applies to all ages and every medical field. Another question we hear is, “How do you know when you’re using an excessive amount of medical care?”. In order to understand this limit, you have to break it down into three components. You can reach an initial limit when a treatment becomes ineffective. Artificial nutrition to extend the life of a person suffering from advanced dementia is one example. This limit can be objectively recognised.

The third limit is reached when the cost is excessive compared to the benefit the treatment provides the patient. That doesn’t mean it’s reached the level of excessive treatment, however. This is the most controversial limit. It’s important we recognise it as such. We might go beyond these limits because our hopes can be unrealistic. Our interventions might try to achieve a specific goal that patients don’t actually want or trample their priorities to promote our own. Our priorities might become mixed up – one example is the temptation to prescribe patients medications to show we haven’t given up. Our kindness can become a trap that lures us into thinking we’re doing good simply because we want to do good. It’s important to analyse what’s going on. In any case, understanding the situation is a good first step towards addressing it.

A second limit is reached once care becomes disproportionate. This means that while the treatment does have an effect, it is too insignificant or uncertain to justify the burden it places on the patient. One example is the use of In order to help teams facing these difficult mechanical ventilation when a person is in a state questions, the CHUV Clinical Ethics Unit is they wouldn’t have wanted and won’t be able partnering with the Training Centre to offer to recover from. This limit is not objective. It interdisciplinary workshops on request. The partially depends on each person’s priorities. first few sessions will focus on essential topics that have cropped up during consultations, including futility, a patient’s decision-making capacity, shared decisions and disagreements over the care plan, quality of life, the use of physical or medical means of coercion, and vulnerabilities. Participants will receive a training certificate at the end of the programme. A Certificate of Advanced Studies (CAS) in PROFILE Samia Hurst is a bioethicist Ethical Leadership in Health Organizations is also and physician who also being offered. Above all, we hope these initiatives works as a consultant for the will provide employees with better tools to deal Clinical Ethics Council at with one of the most complex and difficult facets Geneva University Hospital (HUG). She manages the of our profession. ⁄

CHUV Clinical Ethics Unit and directs the Institute of Ethics, History, and Humanities (IEH2) at the Geneva Faculty of Medicine.

NEW OPPORTUNITIES FOR SOUNDER SLEEP Nearly one-third of the Swiss population suffers from trouble sleeping. Scientists are developing techniques that combine connected applications with robotics to combat this serious problem. TEXT: JULIEN CALLIGARO

ot long ago, Emilie Ostertag, 31, Hospital (CHUV) and associate professor struggled to stay awake while at UNIL. The HypnoLaus cohort study, watching TV or finishing a film. which was conducted in the Lausanne “Even in the middle of the day, while I region on over 5,000 people between was at work or eating, I would become 2009 and 2013, revealed that 49% of men incredibly tired. In the car, I’d have to and 23% of women had over 15 episodes stop regularly to take quick of apnea per hour of sleep. naps.” The Geneva native’s constant state of exhaustion Another figure speaks to the also impacted her social life: trouble the Swiss have with “When I went out with my sleeping. Nearly one-third of friends, I was always the first the population has trouble to go home!” Two years ago, falling asleep or suffers from after a visit to her doctor for insomnia according to the severe chronic headaches, Swiss Federal Statistical Office. Emilie Ostertag discovered The prevalence of this problem she suffered from hypopnea, increases with age: 25% of or moderate sleep apnea. people aged 15–34 are affected, The percentage of This sleep disorder is but this figure increases to 40% the Swiss population characterised by a partial for people aged 65 and older. that regularly uses obstruction of the pharynx, A study out of the University sleeping pills. which reduces airflow by of Basel suggests the use of over 50% for at least ten electronic devices decreases seconds. This in turn decreases blood sleep duration and increases sleep oxygen levels or momentarily awakens disorders. CHUV physician Raphaël the person from sleep. Heinzer estimates that one out of two people could experience at least one “Sleep apnea is more common than you episode of insomnia in their lifetime. would think,” says Raphaël Heinzer, senior physician at the Sleep Investigation and In addition to consequences on their Research Centre at Lausanne University personal and professional lives, including

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“We have lost an hour and a half of sleep in the past century,” says Raphael Heinzer, senior physician at the Sleep Investigation and Research Centre at CHUV and associate professor at University of Lausanne.

forgetfulness and a drop in concentration and performance, sleep disorders also affect health. “Repeated asphyxia over night, which occurs because of apnea, forces the heart to work more intensely at the exact moment when it lacks oxygen,” explains Raphaël Heinzer. People suffering from apnea have a stroke risk that’s two times The proportion higher than the general population. of the Swiss The condition could also exacerbate population that suffers from trouble metabolic diseases such as diabetes. It sleeping. also increases their risk of depression.

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ANTI-INSOMNIA ROBOT

Where does this problem come from? According to Raphaël Heinzer, the answer has to do with our lifestyle. “Over the past 100 years, we’ve lost an hour and a half of sleep. Today, this problem is even worse because the pressure to perform well is much higher than before. We sleep less to work more or have more leisure time.” Our expectations towards sleep have also CORPORE SANO

DECODING

changed. “We want to control everything, including the way we sleep. This is due in part to the media attention sleep disorders have received and the scientific breakthroughs that have occurred in this field in the past 20 years. However, the more we try to control our sleep to perform better the next day, the harder it is to fall asleep.” The specialist doesn’t recommend using electronic devices to measure your sleep. “They aren’t accurate and don’t help you sleep. You are a much better judge of your sleep quality.” There are treatments to help people suffering from sleep disorders have a better quality of life. Psycho-physiological insomnia can be treated with medication. This type of disorder is triggered after a severe bout of insomnia caused by a difficult life event. Some people develop a form of anxiety focused on not being able to sleep and struggle to fall asleep as a result. In this case, Raphaël Heinzer

85+

People aged 85 and older have trouble sleeping twice as often as young people between the ages of 15 and 24 (36% compared 19%).

recommends cognitive behavioural therapy. “It consists of simple techniques that aim to reorganise your sleep, such as temporarily restricting the time you spend in bed,” explains the specialist. “It also involves working with a psychologist to get rid of the negative association you have with your bed and regain confidence in your ability to sleep.”

A Dutch start-up out of the University of Delft, Robotics Institute, is turning to technology to offer a solution. It has developed a robot, called “Somnox”, to improve sleep quality. The machine consists of a peanut-shaped cushion that inflates and deflates, thereby imitating the breathing pattern of a sleeping person. The user will unconsciously emulate the same respiratory rhythm as the robot and fall asleep more quickly. Somnox was presented in early 2018, and the first deliveries are planned for the end of the year. AN APPLICATION TO DETECT RISK

There are already several solutions to reduce sleep apnea. Ventilators, known as CPAP (continuous positive airway pressure) machines, deliver air to your airways using a mask that covers the nose alone or nose and mouth. This pressure keeps the airways from closing, thereby preventing apnea. For less severe cases, aligner therapy is preferred. This device pulls the lower jaw forward during sleep to open up the trachea. New techniques are being developed as well: “Most cases of apnea occur when you sleep on your back,” says Raphaël Heinzer. A start-up recently designed a chest band that vibrates whenever you’re in this position. Little by little, users learn to not sleep on their backs. CORPORE SANO

Another method consists in the installation of an implant stimulating the nerves controlling the respiratory functions. This is the principle of the “Inspire” system, used to treat obstructive sleep apnea. Analyzing the patient’s breathing, the device sends impulses to the hypoglossal nerve, in charge of the movements of the tongue and muscles related to the airways. “This treatment should only be used in the toughest cases when the patient has trouble tolerating the ventilator,” says Raphaël Heinzer. Advancements are also being made in diagnostic techniques. To avoid spending nights analysing patients’ sleep, a costly procedure with limited availability, Heinzer’s team developed a testing tool. The NoSAS score, which is also available via a smartphone app, allows researchers to determine an individual’s risk for sleep apnea. The survey focuses on five factors: neck circumference, body mass index, sex, age, and snoring. “If the total is below eight points, the risk for sleep apnea is excluded with a certainty of 90% to 95%,” says the specialist. “Above eight points, we recommend the patient consult a doctor, who can schedule a sleep test if he or she deems it necessary.” ⁄

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37 RESEARCH

In each issue, “In Vivo” shares the work of a team of researchers from the Faculty of Biology and Medicine of the University of Lausanne.

NIKO GELDNER

Associate professor in the Plant Molecular Biology Department at the University of Lausanne (UNIL).

Increasing plant performance by altering water tightness TEXT: WILLIAM TÜRLER

iscovered over 150 years ago, the Casparian strip is an impermeable structure within the endodermis, a cellular feature that surrounds the central vein inside a plant root. These microscopic nets allow plants to optimise the filtration of soil nutrients and the transport of water. They also protect against various pathogens present in the ground. The team of Niko Geldner, associate professor in the Plant Molecular Biology Departare a wide range of future applications for ment at the University of this research. By altering the development Lausanne (UNIL), decided to of the endodermis, scientists could create “break apart” these structures plants that are more drought resistant, require in a specific way by creating a mutant plant called “Schengen3”. smaller amounts of fertiliser, or are better able to fend off pathogens. All vascular plants, “Our goal is to identify as many including fruit-bearing plants, trees, bushes, genes as possible that are grasses, grains, and ferns, have responsible for the development to the way roots gather the Casparian strips. of the endodermis and undernutrients they need. We must stand how these genes work have a thorough understanding This research opens the door to together to create the Casparian great opportunities in the field of of plants’ regulation systems strip,” says Niko Geldner. to know how to use water agriculture. “We hope our work will lead to a re-evaluation of our and fertiliser in poor or contamiThe work of the Lausanne-based nated soils.” ⁄ models, especially with respect team is advancing quickly. There

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LAB

MEMORISATION: AN ELITE-LEVEL SPORT TEXT PATRICIA MICHAUD

JUST LIKE ATHLETICS OR FOOTBALL, MEMORISATION HAS ITS OWN WORLD CHAMPIONSHIP. ANYONE WHO WANTS TO TAKE PART IN THE COMPETITION HAS TO TRAIN HARD. ONE TACTIC USES METHODS BASED ON IMAGES AND ASSOCIATIONS. BUT COULD THESE EXERCISES ALSO PREVENT COGNITIVE AGEING? WE TAKE A CLOSER LOOK.

Nelson Dellis has won the American memory championship four times.

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MULTIPLE MEMORIES

NELSON DELLIS

reen desks are aligned with military precision, in sharp contrast with the informal clothing worn by the dozens of people seated in the rows. Many are sporting tracksuits, some are wearing baseball caps, and most have noise-cancelling headphones. With heads bowed and shoulders hunched, they are utterly focused on their task. In 2017, the city of Shenzhen hosted the World Memory Championships, a three-day competition in which participants from over 30 countries go head-to-head every year. The competitors wrestle with endless lists of words, associations of names and faces, card decks, and numbers to memorise. Munkhshur Narmandakh won the event in China, becoming the first woman to win since the contest was created in 1991 by the father of mental mapping, Tony Buzan, and chess Grandmaster Raymond Keene. The young, 18-year-old woman from Mongolia successfully memorised the order of 37 decks of cards, or 1,924 cards in a row. Called mnemonists, these memory athletes are becoming increasingly numerous. According to estimates, there are tens of thousands of such individuals in Asia, where television shows like “The Brain” have amassed quite a following. To join the ranks of the international elite of this discipline, called “memory CORPORE SANO

sport” by its adepts, competitors do indeed have to train themselves like any other high-level athlete. Interestingly, the ability to boost one’s memory isn’t limited to a handful of geniuses. For example, a study published in 2017 in the journal “Neuron” showed that anyone can significantly improve their memory by regularly practising the “place” method (see inset). Nevertheless, according to Françoise Marie Thuillier, president of the French Memory Sports Council, participants do share some characteristics. “In Asia, there are quite a few excellent competitors who are in their twenties or even younger. In France, the average age is around 30. They are often brilliant and multi-lingual engineers, lawyer, or researchers. I’ve also met a number of people who don’t meet this stereotype and who are always very endearing.”

“I remember the time I knew what happiness was/Let the memor(ies) live again” – those are the lyrics of Barbara Streisand’s famous 1981 song. In fact, there are several types of memory. The five most well-known types are: Working memory: This is a short-term form of memory that lets you retain and use information for the time it takes to perform a task, such as dial a phone number.

Perceptive memory Also known as sensory memory, this type lets you remember smells, sounds, places, etc.

Procedural memory This lets you remember how to do things (drive, eat, etc.)

ALL AGES

Like the authors of the study published in “Neuron”, Françoise Marie Thuillier notes the methods used by memory athletes, which focus on images and associations, are accessible to everyone when reduced to their simplest form. They make it possible “to learn things, such as a language, more efficiently, and increase concentration”. The specialist gives three recommendations to improve your memory: practice the “place method”, use mental images and create haikus. These short PROSPECTING

Semantic memory This memory concerns definitive knowledge (capital of a country, number of months in a year, etc.)

Episodic memory: Also called autobiographical memory, this type of memory has to do with personal memories (family vacations, first break-up, etc.)

Japanese poems celebrate the present and make you “be creative while appreciating the current moment”. An enthusiast of Japanese culture, Thuillier stresses that enjoyment – especially when it comes to learning – is essential. The Swiss Memory Training Association (Schweizerischer Verband für Gedächtnistraining, SVGT) reports similar findings: “It’s a proven fact. Learning is not just a cognitive process but also an emotional one,” says Margit Bittmann, an executive officer with the SVGT. In fact, the practitioners who work under the association strive to offer their clients “holistic support that takes into account their environment and lifestyle.” Located on the opposite side of the spectrum from memory sport, the goal in this context is quality as opposed to speed and quantity. “Our clients are of all ages and have all kinds of needs. They range from school children who are having a tough time learning their lessons and seniors who lose their keys too often to victims of brain injuries.” So, does memory training stave off cognitive ageing? “I would put it differently,” explains Bittmann. “It lets you apply strategies to combat the problems caused by mental ageing.” To do this, the coaches at the SVGT rely heavily on images and associations, just like mnemonists. However, the head of the association emphasises that memory is just one piece of the puzzle: “To maintain CORPORE SANO

an alert mind, you have to go through the world with curiosity and take on new things, no matter your age.”

A HEALTHY LIFESTYLE, FIRST AND FOREMOST

Chief neuropsychologist at the Leenards Memory Centre at Lausanne University Hospital (CHUV), Andrea Brioschi Guevara also emphasises the important role stimulation plays in maintaining good cognitive function as a result of cerebral plasticity. Many studies have shown the latter is strongly associated with cognitive reserve, or the collection of knowledge and cognitive gains you accumulate throughout your life. As a result, we can say that reading, studying and practising cultural activities “as well as exercising and having regular and enjoyable social interactions” help delay cognitive ageing. Conversely, research into cognitive training has not

yielded a definitive answer in and of itself. “This training must be part of a more comprehensive approach aimed at adopting the healthiest lifestyle possible.” In this context, Andrea Brioschi Guevara points out the benefits of a good diet – based on the Mediterranean diet, if possible – and high-quality sleep. “This isn’t just good advice for seniors. Researchers have noted that if you ask a teenager to memorise a list of words at 9:00 p.m. and have him or her recite the words again at 9:00 a.m., the child’s performance is better than if he or she memorises the list at 9:00 a.m. and is tested at 9:00 p.m.” Indeed, sleep “makes it possible to consolidate what was learned and clean out your cells”. Physical exercise has the same effect. “I think a great thing you can do for elderly people who live alone is to encourage them to get a dog. That way, they will have to go for walks, run errands and keep up a rhythm. Plus, they’ll also be able to meet other people!” ⁄

A MEMORY PALACE The “place method”, also known as the “method of loci” or a “memory palace”, is said to have been invented in ancient times by the Greek poet Simonides of Ceos. This technique, which is a favourite among mnemonists, pairs information you want to memorise with known places. If you want to memorise a series of numbers in a given order, you could mentally visualise each number in a specific place in your (actual) house, then imagine walking through the rooms. When you want to remember the list of numbers, all you have to do is retrace your steps.

PROSPECTING

FRANÇOISE NINANE Deputy Director of Healthcare, CHUV

Forensic medicine proves its worth

Forensic medicine also takes care of the living, especially when it comes to helping victims of violence. It is becoming increasingly proficient at it, in fact, as evidenced by recent developments on both the local and national level.

Another significant change is the inclusion of nursing into the field of clinical forensic medicine in Switzerland. While the idea of nurses in clinical forensic medicine is novel in Switzerland, it’s important to remember that the International Association of Forensic Nurses was founded in 1991. Nowadays, in the United States and in other industrialised countries, forensic nurses practise in every field of forensic medicine and earn a university degree in advanced nursing. This is not yet the case in French-speaking Switzerland, but clinical forensic nurses do follow a four-year post-graduate programme similar to a Certificate of Advanced Studies called “Forensic Aspects and Care in Interpersonal Violence”.

WILLY BLANCHARD

In 2006, Lausanne University Hospital founded a forensic office for victims of physical violence, including conjugal, sexual and street violence, called the Violence Medical Unit (UMV). These services help the victim make the shift from someone who was injured or traumatised to a person who can assert There is more and more interest in this his or her legal rights in court. It also discipline in both French- and German-speakactively listens to patients and refers them ing Switzerland. In fact, the Swiss Association to the appropriate support services when Forensic Nursing was created in 2017. Shortly necessary. Though it was initially planned to after, the Swiss Society of Forensic Medicine be built in Lausanne, the office now has (Société Suisse de Médecine Légale) created three branches throughout the canton a national working group tasked with studying of Vaud to offer victims more local support. the prospect of forensic nursing in Switzerland. As recommended by the World Health Organization (WHO), forensic medical A forensic medical office enables victims of care must be accessible. violence to receive the care and support they The Swiss health authorities are need to treat their injuries. At the same time, supporting this development. and in the same place, patients also receive legal documentation of the trauma they experienced, i.e. the evidence needed to pursue the case in court. Professionals and authorities are committed to offering services that are ever more adapted to the specific needs of victims of violence to ensure they are cared for, supported and defended. ⁄

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COMMENTARY

That’s why these South African amphibians have long been a favourite subject in laboratories. “In the 1950s, they were used to conduct pregnancy tests,” explains the scientist. “They were injected with the urine of the woman being tested, and if the animal laid eggs within 12 hours, the test was positive.” Later on, “Xenopus” ovocytes, which were easier for researchers to work with due to their relatively larger size (1 mm in diameter) and the CORPORE SANO

NAME XENOPUS LAEVIS SIZE 8 TO 15 CM CHARACTERISTICS CARRIES EGGS ALL YEAR ROUND

The frog who laid the golden egg This batrachian of South African origin is used to research gene expressions. TEXT: MARTINE BROCARD

FAUNA & FLORA

fact that they grew on the outside of the animal, were used to study embryonic development. The frog is now used to research gene expression, specifically with respect to the manufacturing of molecules, such as proteins, based on the information contained in DNA. “We inject the genetic information for the protein we want to study into the ovocytes. Two days later, the proteins are ready, and we can work with them for around a week,” says Stephan Kellenberger, who studies ion channels, proteins that play a critical role in the nervous system. In addition to molecular biology, the African clawed frog is especially useful in pharmacology, especially when it comes to testing the mechanisms of action of certain medications. Finally, its tadpoles have started to be used in recent years in environmental toxicology to study the presence of endocrine disruptors in water. ⁄

JOE BLOSSOM / ALAMY

hat makes “Xenopus laevis” so special? Isn’t it just another frog? If you ask a scientist, the answer is a definite no. “They’re unusual because they carry eggs for the entire year, whereas local frogs only do so during their period of reproduction,” explains Stephan Kellenberger, senior lecturer at the Faculty of Biology and Medicine at UNIL (University of Lausanne).

CURSUS

COMMENTARY

CURSUS

psychiatric disorders. This has made diagnosis faster and more reliable, opening the path to new therapeutic approaches and Jean-Daniel Tissot de-stigmatising patients. Dean of the Faculty of Biology and Medicine at At the Faculty of Biology the University of Lausanne and Medicine (FBM), this revolution can be seen in n the 20th century, which wasn’t the field of schizophrenia through the work of Pr Kim Do Cuénod. too long ago, psychiatry could However, these breakthroughs don’t be summed up with a single mean more traditional approaches will fall word – asylum. People were by the wayside. On the contrary, classical committed indiscriminately without receiving any treatment. psychiatry and “hard science” can coexist while building off each other and helping It was a way to get rid of the the other to advance. Certain changes will problem: “Out of sight, out of mind.” have to be made. Language is one aspect Thankfully, things have changed, knowledge that has changed already. We now talk has improved, the discipline has evolved, about “neurosciences”, whether in reference and the public has also (somewhat) come to clinical, fundamental, or psychiatric to terms with psychiatric disorders. medicine. The term may be a bit of a Mental disease is no longer considered a catch-all, but the advantage is that it breaks shameful obstacle by definition. Nevertheless, challenges remain. By their very nature, down barriers separating the various disciplines, even if it’s just symbolic. psychiatric pathologies are non-quantifiable Practices will also have to change. Patient and intangible since they have to do with care must account for progress in basic the mind and psyche. For patients, this is a research and draw from technological recipe for stigma and suspicion. In 2017, innovations – one example that comes to many people still thought the best way to mind is the NeuroTech platform at CHUV. treat depression is a “swift kick to the rear”. Finally, structures must adapt as well. They are completely wrong, of course. In this respect, the FBM celebrates the In the past few years, research has come to decision of the three UNIL and CHUV the rescue of both patients and physicians. departments involved in this field, namely A type of “biological revolution” has taken place. Advancements in the fields of imaging Clinical Neurosciences, Fundamental Neurosciences, and Psychiatry, to work together and molecular biology have improved and join forces to significantly contribute science’s understanding of the brain and to research, teaching, and patient care. ⁄ revealed the biological reasons for many

SAM

CAREER AT THE CHUV

Biological and cultural revolution

MARIE-CLAUDE BOULET

TANDEM

ESTELLE BEZENÃ&#x2021;ON

CURSUS CURSUS

CAREER AT THE CHUV

n an emergency the patient’s care During critical situations in situation, every and administer them the intensive care unit, nurse action counts. efficiently, and comMarie-Claude Boulet works closely Emergency municate clearly so medicine nurse the team and head with physician Estelle Bezençon. Marie-Claude Boulet physician – in this TEXT: WILLIAM TÜRLER, PHOTOS: HEIDI DIAZ and anaesthesiologist case Estelle Bezenand adult intensive çon – can stay up to care physician Estelle date with the situation Bezençon are well aware of this fact. When their and know how the patient’s health is changschedules align, placing them on the same shift ing. When the opportunity arises and within the in their respective services, they collaborate durscope of her skill set, the nurse can also make ing the resuscitation stage, i.e. the process of tak- suggestions: “I pass along the useful information. ing in patients with life-threatening emergencies. Practically speaking, I’m in charge of getting the patient settled in and monitoring and trackIn fact, both medical professionals took the ing their status based on the priorities in their same interprofessional continuing education care.” She anticipates, prepares and administers class, called “Advanced Life Support”, offered by emergency medicines as prescribed, assists with the emergency service. The training programme a wide range of technical medical acts and carries even won the 2017 “Interprofessionality” award out certain technical tasks. And to make sure the from the Swiss Academy of Medical Sciences. transition to other healthcare providers is seamThis class uses realistic situations, similar to less, Marie-Claude Boulet also coaches her fellow the type of training pilots undergo in flight nurses and auxiliary nurses. simulations, to reproduce the environment in an intensive care room. As for Estelle Bezençon, the physician’s work in the resuscitation room involves both surgical and “We have to develop an understanding of each medical pathologies. “No matter the situation, other and know the role and specific assignments we must work closely with a team of doctors and of each person in order to know how to use our nurses. Each person says what he or she will do, respective skills efficiently,” says Marie-Claude then, once an order is given, it must be acknowlBoulet. “We have to have excellent communicaedged and confirmed as being understood, so tion to determine the priority concerns in the the leader can move on to the next step. Our patient’s care and make sure this approach is collaboration is of course aimed at ensuring the understood and followed by the entire team.” In patient’s well-being and providing care as fast this regard, her role consists of being an effective as possible. This is the goal of the resuscitation follower. This means she must follow the normal step – prioritise cases and move quickly, because course of treatment, anticipate the priorities in people’s lives are at stake.” ⁄

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Recognising addiction medicine Addiction medicine is now recognised as a medical discipline. The Federation of Swiss Physicians (FMH) began certifying healthcare professionals on 1 January 2018 by offering continuing education certification. This training, which is provided by the Swiss Society of Addiction Medicine (SSAM), is aimed at doctors from all specialities who have a special interest in the field and have a clinical practice or are involved in addiction science from a public health perspective. Thanks to the certification, participants can serve as a point of reference within their respective specialities for questions related to addiction. “Too often, addiction is considered a shameful behaviour. The goal of this certification is to help addiction be recognised as a pathology and to encourage more people to undergo treatment,” says Pr Jean-Bernard Daeppen, head physician at the Alcohol Addiction Service at CHUV and director of the Training and Testing Commission for Supplemental Training in Addiction Medicine. EDUCATION

NEWS

Angiography: the future of autopsies Post-mortem angiography, developed by Pr Silke Grabherr, chief of the Swiss Francophone University Centre of Forensic Pathology (CURML), has proven to be better than any other autopsy technique at detecting lesions in the body. Post-mortem angiography is a test used to visualise the blood vessels in a corpse by injecting a contrast agent. According to a study published in the prestigious journal Radiology, an autopsy that’s conducted without post-mortem angiography misses 39% of all indicators and 23% of essential indicators. The study, which was coordinated by Pr Grabherr, was conducted in nine forensic pathology centres throughout Europe, including CURML.

STUDY

Saving time in research For the past three years, the “Pépinière” support programme founded by CHUV and UNIL has been encouraging department heads to identify young clinical managers or associate doctors who deserve a helping hand. “The idea is to fund 50% of the winners’ working time for two years; as they’ll have an amount of time set aside, they’ll be able to do research freely,” explains Jocelyne Bloch, senior physician in the Neurosurgery Service and president of the Pépinière commission. The second round of winners, which was announced at the end of 2017, includes Christel Tran, associate physician at the Genetic Medicine Service, and Antonia Digklia, chief resident in the Oncology Department. Dr Tran is conducting a preliminary study on sialic acid, a simple sugar that plays a key role in brain development. Dr Digklia is investigating a type of immunotherapy, adoptive cell therapy, and its effect on soft tissue sarcoma, a rare disease that represents 1% of cancers in humans.

SUPPORT

CURSUS

NEWS

«Giving young people with autism a real chance» Since 16 January, a young man with autism spectrum disorder has been working at the Lausanne University Hospital’s bakery. Human Resources Manager Antonio Racciatti worked with Autisme Suisse Romande and Pro Infirmis to create this professional integration initiative. INTEGRATION

GILLES WEBER

Why this project? I started this project because during an event organised by Autisme Suisse Romande last year, I became aware of how hard it was for people on the autism spectrum to enter the job market, regardless of their skills. According to a 2011 study by Autisme Europe, an estimated 76% to 90% of adults with autism are unemployed. It seemed clear to me that if there was one employer that could set an example, it was CHUV. Soon after, I reached out to Autisme Suisse Romande and Pro Infirmis. These two groups helped us identify people we could hire and design suitable work places and environments. Since one of these young people was interested in baking, I

naturally turned to my friend and colleague Pierre-Yves Müller, director of the Hospital Logistics Department (LOH), who immediately agreed to take him on.

How does it work, practically speaking? To help this young man integrate in the best possible conditions, we worked with Pierre-Yves Müller to create a stable framework where the team was always the same. An instructor from Pro Infirmis is always by his side to provide support and help raise awareness among his colleagues. Professor Nadia

Chabane, chief physician at the Regional Autism Centre (Centre cantonal de l’autisme), also agreed to offer a training programme to help our employees understand the reactions of people with autism, who often don’t know how to lie and can express themselves very directly. The desire to learn together is one of this project’s strengths. In time, is the goal to integrate other people with autism? In the beginning, I gave the green light to hire one person. However, it turned out this young man has close ties with two other people. I was moved, and the two friends of our new employee should join CHUV in the near future, either with the LOH or elsewhere. Our goal is to give them a real chance. What we hope is that this experience will help them become independent, with a job and a salary just like everyone else. If this first phase goes well, we would definitely want to expand the project, and we hope other employers will follow suit. /

IN VIVO

Magazine published by the Lausanne University Hospital (CHUV) and the news agency LargeNetwork www.invivomagazine.com

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MUSCLE MASS

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IN EXTENSO

The mysteries of puberty